Rabies is not only a public health problem that causes more than 40,000 human deaths per year worldwide but also causes a tremendous economic burden. In the USA alone, more than one billion dollars are spent annually for control, treatment, and prevention of rabies. In developing countries stray dogs are the major carriers of rabies. However, in North America wildlife species, in particular raccoons and skunks, account for more than 90% of all rabies cases. Oral immunization is the most effective method to control and eradicate rabies in stray dogs and wildlife. Unfortunately, the currently available oral rabies vaccine induces insufficient immunity in dogs and skunks, in the initial phase of this research rabies recombinant viruses have been developed by distinct genetic manipulations designed to eliminate pathogenicity and augment immunogenicity. The specific phase II objectives of this research project are to extend safety and efficacy testing of these newly developed rabies vaccines in laboratory rodents and target animals (raccoon and skunk), and to choose a strain for which a master seed stock will be prepared and characterized and a bioreactor process developed for commercial production. PROPOSED COMMERCIAL APPLICATION: The USDA and APHIS, WS are proposing to expand the oral rabies vaccination program designed to stop the advance of rabies and reduce the incidence of rabies cases in selected states in the US. If this research is able to provide a safer, more potent and cost-effective oral rabies vaccine, the new vaccine could potentially supplant the currently used V-RG vaccine in this program.